Adenosine is an important modulator in the brain that regulates cerebral blood flow and neurotransmission and is neuroprotective during pathological conditions such as stroke. The four adenosine receptors have a range of affinities and effects. The concentration of adenosine available to bind to and activate these receptors controls the physiological response to adenosine. Therefore, rapid monitoring of adenosine concentrations is required to understand the time course of the neuromodulatory effects of adenosine. The objective of this proposal is to develop a rapid sensor for monitoring adenosine concentrations in vivo. This sensor will allow an understanding of the real-time concentration profile of adenosine available to activate receptors under physiological and pathological conditions. We plan to carry out these objectives by developing the following aims: (1) Development of carbon-fiber microelectrodes as sensors for adenosine, (2) Development of carbon nanotube-modified sensors for adenosine, and (3) Characterization of stimulated adenosine release in vivo. This sensor will allow the first measurements of rapid modulatory effects of adenosine in the brain and lead to a greater understanding of the dynamics of neuromodulation. [unreadable] This research will lead to a better understanding of the basic neurobiology of how adenosine modulates neurotransmission. The sensor we develop could be used to study how adenosine modulates dopamine release, leading to new treatments for Parkinson disease. The sensor could also be utilized to study the effects of drugs that regulate endogenous adenosine concentrations, which are proposed neuroprotective treatments for traumatic brain injury, seizures, and stroke. [unreadable] [unreadable] [unreadable]